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Post-Transcriptional Regulation of PARP7 Protein Stability Is Controlled by Androgen Signaling
Teddy Kamata1,2, Chun-Song Yang1, Tiffany A Melhuish1
1Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Cells
|February 12, 2021
Summary
Androgen signaling tightly regulates Poly-ADP-ribose polymerase 7 (PARP7) in prostate cancer. Androgen receptor (AR) controls PARP7 transcription and post-transcriptionally stabilizes the protein, impacting its nuclear accumulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Poly-ADP-ribose polymerases (PARPs) are crucial enzymes in cellular processes.
- PARP7, a mono-ADP-ribosyltransferase, exhibits tumor-suppressive roles in various cancers.
- Prostate cancer cells exhibit specific regulation of PARP7 by androgen signaling.
Purpose of the Study:
- To investigate androgen signaling's regulation of PARP7 protein homeostasis in prostate cancer.
- To elucidate the mechanisms of PARP7 regulation by the androgen receptor (AR).
Main Methods:
- Analysis of PARP7 protein half-life under androgen signaling conditions.
- Investigating transcriptional and post-transcriptional regulation by AR.
- Assessing the impact of PARP7 domain mutations on protein degradation.
Main Results:
- PARP7 protein has an extremely short half-life (4.5 min) in prostate cancer cells.
- Androgen signaling significantly increases PARP7 half-life to 25.6 min via post-transcriptional mechanisms.
- Unlike other PARPs, PARP7 shows rapid turnover and androgen-dependent stabilization.
- Mutations in PARP7 domains (catalytic, zinc finger, WWE) decrease its degradation rate.
- Stabilized PARP7 accumulates in the nucleus, its suggested primary site of action.
Conclusions:
- Androgen receptor (AR) signaling regulates PARP7 transcriptionally and post-transcriptionally in prostate cancer.
- This dual regulation ensures tight control over PARP7 protein dosage.
- PARP7 stabilization by androgens may be critical for its function in prostate cancer.
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